Eighty years ago, Peyton Rous was the first to identify a filterable agent that caused tumors in chickens, and it is now known that this agent, Rous sarcoma virus (RSV), is a retrovirus, converting its RNA genome to DNA during its life cycle. Viruses of this type were neglected for several decades, until strains that caused tumors in mammals were isolated. These agents were identified as retroviruses in the late 1960s and 1970s with the discovery of reverse transcriptases and proviruses transmitted in the germ line. 1 , 2 More recently, retroviruses have gained further attention as the presumed causative agents of T cell leukemia and acquired immune deficiency syndrome (AIDS). Indeed, major sections of this chapter will focus on tRNA involvement in the life cycle of the AIDS virus, human immunodeficiency virus, type 1 (HIV-1).